title: Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection.
abstract: Myxovirus resistance A (MxA) is an antiviral protein induced by type I interferons α and β (IFN-α and IFN-β) that can inhibit virus replication. We examined whether the MxA polymorphisms were related to the risk and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C-123A and G-88T polymorphisms were genotyped in two independent case-control populations in China by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). MxA messenger RNA was quantified by real-time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19 patients with EV71 infection. Significantly decreased susceptibility to EV71 infection was observed for the -123A allele and -88T allele carriers, with ORs (95% CIs) estimated as 0.56 (0.39-0.81) and 0.64 (0.47-0.88), respectively, in the northern population. This association was confirmed in the southern population, with ORs (95% CIs) estimated as 0.58 (0.38-0.89) and 0.67(0.47-0.95), respectively. The A- 123T- 88 haplotype was also significantly associated with lower risk of EV71 infection in both the northern (OR = 0.62; 95% CI = 0.44-0.85) and the southern population (OR = 0.63; 95% CI = 0.43-0.92). Furthermore, we observed higher MxA messenger RNA levels in IFNβ1a-stimulated PBMCs from the -123A or -88T allele carriers compared with that from nocarriers. Our findings suggest that polymorphisms in the MxA promoter may play a role in mediating the susceptibility to EV71 infection in Chinese population.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street Fengtai District, Beijing, 100071, People's Republic of China.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Chen
authors.forename: Xiujun
authors.initials: X
authors.lastname: Li
authors.forename: Xianjun
authors.initials: X
authors.lastname: Wang
authors.forename: Shujun
authors.initials: S
authors.lastname: Ding
authors.forename: Renli
authors.initials: R
authors.lastname: Zhang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.forename: Cui
authors.initials: C
authors.lastname: He
authors.forename: Lu
authors.initials: L
authors.lastname: Zhuang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Panhe
authors.initials: P
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Wuchun
authors.initials: W
authors.lastname: Cao
mesh_terms: D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D029821:Enterovirus A, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D005243:Feces / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D064547:Myxovirus Resistance Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D018571:Sentinel Surveillance; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger